Introduction. Our group has recently demonstrated that multiple anesthetic agents inhibit the production of pro-inflammatory cytokines among LPS-challenged rodents. Because anesthesia is fundamental to virtually all surgical procedures, it is important to further elucidate the kinetics of this phenomenon. The purpose of this study was to determine the influence of timing of onset and duration of anesthesia on the down regulation of LPS-induced cytokine production. Methods. Forty 8-week-old, male C57BL/CJ mice were anesthetized for 60 min with isoflurane given at different time points ( n = 10) with respect to the intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 15 mg/kg). Blood samples were collected from all groups via cardiac puncture 1.5 h following LPS injection. Two groups received anesthesia before the LPS injection: 60 min pretreatment and 60 min pretreatment followed by an additional 30 min delay. Two additional groups received the LPS injection at time zero: one received LPS simultaneous to the onset of anesthesia and the final group received LPS only (control group, no continued anesthesia). In a second experiment, 40 mice were given LPS injection simultaneous to the onset of anesthesia but with varying durations of anesthesia (0, 10, 30, and 60 min, n = 10). Results. Compared to the LPS control group, plasma levels of TNF-α were significantly attenuated in the pretreatment plus delay group, the pretreatment group, and the simultaneous group (29.3, 38.6, and 91.8%, respectively; P < 0.05 by Student--Newman--Keuls method). Furthermore, the simultaneous group was significantly lower than the pretreatment plus delay group and the pretreatment group ( P < 0.05). IL-6 production among the pretreatment and simultaneous groups was virtually abolished compared to the LPS control group (77.4 and 100% inhibition, respectively; P < 0.05 via SNK). A significant dose-response relationship was found between the duration of anesthesia (0, 10, 30, or 60 minutes) and the attenuation of TNF-α and IL-6 production ( P < 0.05 for both cytokines). Conclusions. Anesthesia inhibits the production of proinflammatory cytokines among LPS-challenged mice. This phenomenon is greatest when the anesthesia is administered simultaneous to the LPS challenge and when the duration of anesthesia is the longest. Rather than simply being a means to an end, anesthesia may prove useful as a therapy in its own right for the treatment of critically ill patients.